Saliva diagnosis of concussion (4/1/21 newsletter)

Apr 8

We would like to acknowledge our volunteers and leadership team members who wrote for this newsletter:

Writers: Will Altaweel, Conor Gormally, Malayka Gormally, Ming Shen, Emily Spain, Trinh Tieu, Rainey Tilley, and Josh Wu.

Editors: Conor Gormally and Malayka Gormally.

Do you find the Concussion Update helpful? If so, forward this to a friend and suggest they subscribe.

Opportunities

April 7, 10:30 - 11:30 am, PST, Modified Gentle Yoga for Brain Injury, free Zoom class. Presented by the Brain Injury Alliance of Washington State (BIAWA). Register in advance.

April 8, 3:30 - 5:00 pm PST, “Ask Lori”: Q&A on Relationship Challenges After Brain Injury, free Zoom program. Presented by the BIAWA. Register in advance.

April 13, 6:00 - 7:00 pm EST: Exercise Therapy with Mark Bayley, MD, Medical Director of the Brain and Spinal Cord Rehabilitation Program at the Toronto Rehabilitation Institute, University of Toronto. This free Zoom program is hosted by the Canadian Concussion Centre. Register in advance.

Education

Free webinar series for general practitioners and ED doctors: concussion assessment and management

The Australian College of Sport and Exercise Physicians (ACEP) is offering a free webinar to assist general practitioners and emergency doctors with the proper assessment of concussions in both young and adult patients. A panel of sports doctors, including ACEP fellows and Dr. Martin Raftery, the Medical Director of FPES Australia and 2011-2020 Chief Medical Officer at World Rugby, will be speaking during the webinar.

Speaking with newsGP, Dr. Raftery asserted that it is integral for general practitioners to understand the management and prevention of head injuries, as “‘head injuries are a societal problem,’” given that only 20% of head injuries treated at emergency departments are due to sports.

The panelists in the webinars, which will be held between March 16 and July 1, 2021, will be going through the concussion symptoms as well as the best ways to assess concussions and offer advice to patients. Registration for the webinar can be found here.

Sports

Longer recoveries for athletes who continue playing after a concussion or delay reporting a concussion

Mitchell Barnhart et al. performed a systematic review and meta-analysis of studies in the last ten years that explored the relationship between delayed reporting and recovery times in athletes with concussion. Their review, published in Sports Medicine, examined 12 studies that met their standards of statistical rigor and evidence strength and focused on “immediate versus delayed reporting or early versus late presentation following a concussion.”

The authors found that athletes who immediately reported their concussions recovered approximately 5.4 days faster than those who delayed reporting their injury. Those who reported immediately also had lower symptom scores and postconcussion symptom burdens than delayed reporters. Their qualitative analysis also showed that “patients who presented earlier to a concussion specialist tended to recover faster than those who presented later.”

Diagnostics

MicroRNAs in saliva can predict concussion with high accuracy - results only available through lab processing

Researchers have found that the expression levels of several microRNAs found in saliva can differentiate “concussed patients from all controls” with 96% accuracy in professional male athletes, according to an article in Healio. Further research should assess the test’s accuracy with different populations - females, youth, and others. While labs can only currently process the saliva test, lead author Dr Valentina Di Pietro told The Guardian that the technology to make the test available on the playing field “could be developed within three to five years.’

Over two years, researchers in Birmingham, UK, took preseason baseline saliva samples for 1028 senior male professional rugby players. The researchers then took saliva samples during “standardised head injury assessments (HIAs) at three time points (in-game, post-game, and 36–48 hours post-game).” They also collected saliva samples from two control groups: uninjured players and players who sustained a musculoskeletal injury.

The study, published in the British Journal of Sports Medicine, identified a panel of 14 microRNAs that “accurately predicted clinical diagnosis of concussion in professional rugby players.” Researchers theorize “that saliva can receive exosomal miRNAs directly from cranial nerves in the oropharynx, and as such there is a rapid response within saliva after TBI, making them particularly suitable for a pitch-side diagnosis.”

In her blog post about this study, Julie Stamm, PhD, mentions that “some of the microRNA biomarkers may recover to baseline levels quickly, while others may linger.” It is still unknown if this saliva test will be accurate several hours or days after the injury.

Self-care

Study sheds light on the importance of sleep for concussion recovery

A study conducted by Juan Piantino et al. found that poor sleep may hinder the clearance of perivascular waste in the brain, a process that plays a vital role in healing concussions. The study, published in the Journal of Neurotrauma, included 56 Iraq and Afghanistan veterans who sustained a concussion and used MRI to measure the volume of perivascular spaces (PVS) in their brains. PVS volume serves as an indicator of the brain’s waste clearance functioning; an increased PVS volume indicates impaired waste clearance.

The authors found a significant association between poor sleep and increased PVS volume. Moreover, they found a positive correlation between PVS volume and postconcussive symptoms. These findings suggest that poor sleep may contribute to impaired perivascular waste clearance, which may lead to worse postconcussive symptoms.

Regarding the findings, Piantino commented, “this study suggests sleep may play an important role in clearing waste from the brain after traumatic brain injury—and if you don’t sleep very well, you might not clean your brain as efficiently.”

Therapies Currently Available

Still not enough research to make a definitive ruling on current concussion medications

Are there medications - pharmacological interventions - that reduce the symptom burden for patients with mild traumatic brain injury? Charles Feinberg et al. performed a systematic review of research articles published between 2010 and 2020, published in JAMA Neurology. Of 1495 studies, only 23 publications met their inclusion criteria. These 23 articles addressed 20 medications, with only five used in more than one study: methylphenidate, sertraline hydrochloride, ondansetron, amitriptyline, and melatonin.

Sixteen of the studies reported “symptom burden reduction,” associated with taking the medication under research. However, the findings of reduction of symptom burden were not consistent between the studies. “None of the pharmacological interventions examined were consistently associated with symptom burden reduction across the studies in the review.” The authors identified the limited number of high-quality studies on this topic and suggested standardization of clinical assessment measures for future studies.

Veterans and Service Members

VA collaboration develops new program to help veterans with brain injury - Concussion Story Wall

The Federal News Network interviewed Dr. Odette Harris and Dr. Molly Timmerman on the VA's new program to help veterans struggling with traumatic brain injuries. The Veterans Health Administration's Center of Excellence in Palo Alto has collaborated with TeachAids to create the Crash Course Concussion Story Wall for veterans and others to share their experiences with brain injury.

The Wall currently consists of approximately 4,000 personal videos: sports celebrity stories, injury stories, family members' stories, and medical experts' perspectives. You can search the Wall for the injured person's or the family member's perspective, as well as the cause of injury, symptoms, topics, gender, age, and the number of concussions experienced.

Dr. Harris noted that "there's a lot of evidence in our peer reviewed literature that the phenomenological component of one's experience, the patient's experience, of the storytelling component is significantly contributory to their recovery." Since brain injuries are often invisible injuries, Dr. Timmerman explained that these storytelling opportunities can be highly impactful for patients.

In addition to this storyboard helping the patient experience, researchers are performing a qualitative study to analyze persistent symptoms of concussion in patients. Dr. Timmerman noted that this research will be beneficial "both from a scientific perspective, and also as a clinician."

The production of the Concussion Story Wall was the work of 1,500 volunteers over 2.5 years. Additional collaborators include The Brain Injury Association of America, the National Council on Youth Sports, and others.

Mental Health

Fear-avoidance behavior may be a clinically-relevant area of study after mTBI

A study by Dr. Molly Cairncross et al., published in The Journal of Head Trauma Rehabilitation, attempted to create baseline data for fear-avoidance behavior following concussion. The authors collaborated with five concussion clinics across Canada. Five hundred sixty-three adults came into the clinics to be assessed for a concussion, completing the relatively new FAB-TBI (Fear-Avoidance Behavior after TBI) questionnaire alongside two standard measures of postconcussion symptom burden: the Rivermead Postconcussion Symptoms Questionnaire and the Sport Concussion Assessment Tool-5 (SCAT-5).

The authors found that female concussion patients reported more fear-avoidance behavior than male patients, indicating that sex-stratified baselines are likely necessary for accurate assessment. Additionally, loss of consciousness and higher symptom burden were also statistically associated with higher FAB-TBI scores, though time since injury was not. While this study’s focus was primarily on data-gathering, the authors conclude that their exploration supports current clinical interpretations of fear-avoidance behavior and will hopefully spur further research into this area.

Women's Health

High levels of progesterone can reduce stress after concussion, speed recovery in females

A Northwestern press release posits that higher progesterone levels can reduce stress levels following a concussion, therefore expediting recovery in females. The article opens with the question, “Could birth control pills help females recover faster from concussions and reduce their symptoms?” The release summarizes the findings from a 2021 pilot study by Yufen Chen et al., published in the Journal of Neurotrauma. Chen and colleagues sought to examine the relationship between hormonal fluctuations caused by the menstrual cycle or hormonal contraceptives and cerebral blood flow following a mild traumatic brain injury (mTBI).

Three to ten days following an mTBI, the authors measured the cerebral blood flow in female athletes and then administered a perceived stress assessment. Chen and colleagues found a significant relationship between progesterone levels, cerebral blood flow, and the perceived stress score in the concussed female athletes. Specifically, the left middle temporal gyrus was the region that showed blood flow closer to normal levels (more normative) in females with higher levels of progesterone.

The Northwestern press release explains that the left middle temporal gyrus integrates visual and auditory stimuli and is associated with social anxiety disorder. Thus, a more normative blood flow to this region following a concussion would indicate decreased perceived stress levels following injury.

Chen and colleagues’ study is promising, as it identifies higher levels of progesterone due to the menstrual cycle or hormonal birth control as a potentially protective factor against increased levels of stress following an mTBI in females. Since this was a pilot study, more data is needed to determine the significance and replicability of Chen and colleagues’ results. Nonetheless, their results are promising and pertinent, as more research is needed surrounding mTBI in females.

Culture

Judge dismisses lawsuit claiming racial discrimination in concussion settlement, orders mediation

A federal judge dismissed a lawsuit alleging that the NFL’s concussion settlement is racially discriminatory against retired players, as reported in ABC News. However, concerns over NFL protocol around “race-norming” and adjusting players’ cognitive test scores remain. The judge ordered a mediator to address these concerns, according to a New York Times article. The two NFL players who filed the racial discrimination case, Kevin Henry and Najeh Davenport, are seeking new legal representation for the mediation, saying the attorney representing NFL players has known about race-norming since 2018 and did not take action.

Former NFL players Henry and Davenport both suffered from long-term symptoms of concussions. They sought compensation through the NFL Concussion Settlement program for the damages they had incurred during their careers. After being seen by neuropsychologists to confirm their symptoms of cognitive decline and determine their eligibility for compensation, they submitted applications into the program but were denied.

Usually, a player’s cognitive impairment was measured by comparing their current cognitive test score to the average score. However, Henry and Davenport’s scores did not qualify because they did not undergo a “full demographic correction” where their scores were compared to the average or norm of similar demographic groups, then adjusted by race. This practice, also known as “race-norming,” compares individual’s scores among the average of their own demographic.

Former players say that the norms in the NFL’s concussion settlement program manual assume that the average Black player starts at a lower level of cognitive function than the average white player at the outset of their careers. Therefore, Black players must show greater cognitive declines than white players to qualify for compensation.

The NFL says it is up to the clinician’s judgment whether or not to consider race in adjusting test scores. However, according to ABC News, there are conflicting reports from players and clinicians alleging that the “race-norming” corrections are mandatory.

CTE and Neurodegeneration Issues

Consensus diagnostic criteria for diagnosing CTE in the living – for research purposes

The Washington Post wrote an article about a new research paper that documents the first consensus criteria to diagnose chronic traumatic encephalopathy symptoms (CTE) among living people. This paper, by Douglas I. Katz et al. and published in Neurology, marks a monumental milestone in the diagnosis of CTE. Historically, CTE could only be diagnosed after death, making it a poorly understood disease. However, through this new research paper, four factors have been identified to aid in CTE diagnosis. These factors are repetitive head impacts, cognitive impairment, a pattern of deterioration, and no clinical explanation for a patient’s condition.

This publication is just the beginning of diagnosing CTE. Robert Stern, an author of the paper, states that the identification criteria for CTE are geared toward researchers with the goal of streamlining future research. This research is also a step toward differentiation from other neurological diseases (like Alzheimer’s) and toward the discovery of a biomarker for CTE. With the synergistic advancement in biomarkers, blood tests, and CTE diagnostic specification, the future looks hopeful for eventually diagnosing CTE in the living in a clinical setting.